Donepezil ER Tablets

Uses

Amoxicillin is used for the treatment of the following bacterial infections when caused by susceptible organisms:

• Respiratory tract, ENT infections: Acute and chronic bronchitis, pneumonia, otitis media, sinusitis, tonsillitis, pharyngitis & laryngitis, lobar & bronchopneumonia, chronic bronchial sepsis.
• Urinary tract infections: Pyelonephritis, cystitis and urethritis.
• Obstetric & gynaecological infections: Bacteriuria in pregnancy, septic abortion, intra-abdominal sepsis and puerperal sepsis.
• Gastro-intestinal infections: Typhoid and paratyphoid.
• Skin & soft tissue infections: Cellulitis, infected wounds and abscesses.
• Generalized infections: Septicemia, bacterial endocarditis, meningitis, peritonitis and osteomyelitis.
• Venereal infections: Gonorrhea and syphilis. Amoxicillin may also be used as prophylactic cover for patients at risk of developing endocarditis when undergoing dental surgery.

Lansoprazole is used for:

• Short term treatment of active duodenal ulcer
• Maintenance of healed duodenal ulcers
• Short term treatment of active benign gastric ulcers
• Short term treatment of active erosive esophagitis
• Maintenance of healing of erosive esophagitis
• Pathological hypersecretory conditions including Zollinger- Ellison Syndrome
• H. pylori eradication to reduce the risk of duodenal ulcer recurrence

Donepezil ER Tablets is also used to associated treatment for these conditions: Acute Bacterial Sinusitis (ABS), Acute Otitis Media, Acute Otitis Media (AOM), Bacterial Infections, Community Acquired Pneumonia (CAP), Duodenal ulcer caused by helicobacter pylori, Genitourinary infections, Helicobacter Pylori Infection, Lower Respiratory Tract Infection (LRTI), Peptic Ulcer With H. Pylori Infection, Sinusitis, Skin and Subcutaneous Tissue Bacterial Infections, Urinary Tract Infection, Acute, uncomplicated Gonorrhea, Ear, nose, and throat infectionsGastro-esophageal Reflux Disease (GERD), Gastrointestinal Bleeding, Helicobacter Pylori Infection, Peptic Ulcer Disease, Hypersecretory conditions

How Donepezil ER Tablets works

Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action.

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets.

Dosage

Donepezil ER Tablets dosage

Ear/Nose/ThroatInfection (Mild to Moderate):

• Adult:500 mg every 12 hours or 250 mg every 8 hours
• Children:25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

Ear/Nose/ThroatInfection (Severe):

• Adult: 875 mg every 12 hours or 500 mg every 8 hours
• Children: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Lower respiratory tractInfection (Mild/ Moderate/Severe):

• Adult: 875 mg every 12 hours or 500 mg every 8 hours
• Children: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Skin/skin structureInfection (Mild/Moderate):

• Adult: 500 mg every 12 hours or 250 mg every 8 hours
• Children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

Skin/skin structureInfection (Severe):

• Adult: 875 mg every 12 hours or 500 mg every 8 hours
• Children: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Genitourinary tractInfection (Mild/ Moderate):

• Adult: 500 mg every 12 hours or 250 mg every 8 hours
• Children: 25 mg/kg/day in divided doses every 12 hours or 20 mg/kg/day in divided doses every 8 hours

Genitourinary tractInfection (Severe):

• Adult: 875 mg every 12 hours or 500 mg every 8 hours
• Children: 45 mg/kg/day in divided doses every 12 hours or 40 mg/kg/day in divided doses every 8 hours

Gonorrhea, Acute, uncomplicated ano-genital, and urethral infections in males and females:

• Adult: 3 g as single oral dose
• Prepubertal children: 50 mg/Kg/Amoxycillin, combined with 25 mg/kg Probenecid as a single dose. Since Probenecid is contraindicated in children under 2 years, do not use this regimen in these cases.

Benign gastric ulcer: 30 mg daily in the morning for 8 weeks.

Duodenal ulcer: 30 mg daily in the morning for 4 weeks; maintenance 15 mg.

NSAID-associated duodenal or gastric ulcer: 15-30 mg daily for 4 weeks, followed by a further 4 weeks if not fully healed.

Zollinger-Ellison syndrome (and other hypersecretory conditions): Initially 60 mg once daily adjusted according to response; daily doses of 120 mg or more is given in two divided doses.

Gastroesophageal reflux disease: 30 mg daily in the morning for 4 weeks, followed by a further 4 weeks if not fully healed; maintenance 15-30 mg daily.

Acid-related dyspepsia: 15-30 mg daily in the morning for 2-4 weeks.

Suspension: Shake the bottle well before adding water. Then add 12 tea spoonful (60 ml) of boiled and cooled water to the bottle and shake well to make 100 ml suspension.

Amoxycillin 500 mg Injection:

• Intramuscular : Add 2.5 ml water for injection to Amoxycillin 500 mg injection vial.
• Intravenous : Dissolve Amoxycillin 500 mg injection in 10 ml water for injection.

Side Effects

Side effects are mild, rare and infrequent. As with other penicillins, it may induce diarrhea, indigestion or skin rashes that usually stop during treatment and rarely calls for discontinuation of therapy.

Severe or irreversible adverse effects: The possible induction of carcinoid tumors by profound acid suppression, and a rise in serum gastrin may occur. There is a rise in serum gastrin levels in the first 3 months of treatment, which are then maintained though at a lower level than those found in pernicious anaemia. Long term treatment with a proton pump inhibitor in patients with Helicobacter pylori infection may accelerate the development of atrophic gastritis.

Symptomatic adverse effect: Dose dependent diarrhoea occurs with an incidence of about 4% at 30 mg per day, rising to 8% at 60 mg per day. Headache occurs in 2-3% of treated patients

Toxicity

Patients experiencing an overdose may present with hematuria, oliguria, abdominal pain, acute renal failure, vomiting, diarrhea, rash, hyperactivity, and drowsiness. Treat overdose with symptomatic and supportive treatment, which may include emesis or hemodialysis.

The most commonly reported adverse events occurring more frequently in lansoprazole treated patients compared to placebo include abdominal pain, constipation, diarrhea, and nausea. There is a case report of toxic epidermal necrolysis (TEN), which is a rare but very serious cutaneous reaction, caused by lansoprazole. The previously healthy patient presented with symptoms of TEN 15 days after starting lansoprazole to manage peptic disease. Although the use of PPI's is rarely associated with TEN, causation should be considered if a patient presents with TEN shortly after newly commencing a PPI.

In a single case report, a patient ingested 600 mg of lansoprazole and did not experience any adverse effects or symptoms of overdose. Overall, lansoprazole is well tolerated with relatively few adverse effects.

Lansoprazole is classified as Pregnancy Category B. Although there are animal studies that suggest lansoprazole does not cause harm to the fetus, there is still a paucity of human data. Hence, lansoprazole should only be administered to pregnant women if other options with more safety data have been exhausted.

It is unknown if lansoprazole is excreted in human breast milk. It is worth mentioning that lansoprazole has been used safely in infants, and is therefore likely safe to use during breastfeeding.

Precaution

In renal impairment, the excretion of antibiotic will be delayed and depending on the degree of impairment it may be necessary to reduce the total daily dose.

Gastric malignancy should be ruled out. Hepatic impairment. Pregnancy and lactation.

Interaction

The simultaneous use of Amoxicillin and an oral contraceptive might cause breakthrough bleeding or pregnancy on rare occasions. Concurrent administration of probenecid delays the excretion of Amoxicillin.

Lansoprazole appears to be a selective inhibitor of the cytochrome P-450 monooxygenase system; there may be an effect on hepatic clearance, but there have been no reports to date of clinically relevant interactions. There is some uncertainty over the effect of Lansoprazole on the oral combined contraceptive pill. Further assessment is currently underway. Physiological changes similar to those found with Omeprazole are likely to take place because of the reduction in gastric acid, which is likely to influence the bacterial colonization of the stomach and duodenum and also vitamin B12 absorption.

Volume of Distribution

The central volume of distribution of amoxicillin is 27.7L.

The apparent volume of distribution of lansoprazole is 0.4 L/kg.

Elimination Route

Amoxicillin is approximately 60% bioavailable. A 250mg dose of oral amoxicillin reaches a C_max 3.93±1.13mg/L with a T_max 1.31±0.33h and an AUC of 27.29±4.72mg*h/L. A 875mg dose of oral amoxicillin reaches a C_max 11.21±3.42mg/L with a T_max 1.52±0.40h and an AUC of 55.04±12.68mg*h/L.

The oral bioavailability of lansoprazole is reported to be 80-90% and the peak plasma concentration(Cmax) is achieved about 1.7 hours after oral dosing. Food reduces the absorption of lansoprazole (both Cmax and AUC are reduced by 50-70%); therefore, patients should be instructed to take lansoprazole before meals.

Half Life

The half life of amoxicillin is 61.3 minutes.

One source reports the half life of lansoprazole to be 0.9 - 1.6 hours, while another source cites 0.9 - 2.1 hours. The general consensus is that lansoprazole has a short half life and is approximately 2 hours or less. These numbers may be misleading since it suggests that lansoprazole has a short duration of action when in practice, lansoprazole can effectively inhibit acid secretion for ~24 hours due to it's mechanism of action.

Clearance

The mean clearance of amoxicillin is 21.3L/h.

The reported clearance of lansoprazole is 400-650 mL/min.

Elimination Route

125mg to 1g doses of amoxicillin are 70-78% eliminated in the urine after 6 hours.

A reported 14-23% of a lansoprazole is eliminated in the urine with this percentage range including both conjugated and unconjugated hydroxylated metabolites.

Pregnancy & Breastfeeding use

Because of its lack of teratogenicity, Amoxicillin can beused safely throughout pregnancy at the normal adult dose. The small amount of Amoxicillin secreted in maternal milk rarely causes problem in the infant. It can therefore be used safely during lactation in most instances.

Lansoprazole should be avoided in pregnancy unless there are compelling reasons.

Contraindication

Amoxicillin is contraindicated for patients hypersensitive to penicillin, infectious mononucleosis, neonatal period or babies born of mothers hypersensitive to penicillin

Lansoprazole is contraindicated in patients with known hypersensitivity to any component of the formulation.

Special Warning

Neonates:There is no relevant human data. The drug is not recommended for use with neonates.

Children: The youngest person to have received Lansoprazole in clinical trials was 13 years old.

The Elderly: No problems have been encoun- tered in clinical use and there has been no increase in adverse drug reaction in the elderly.

Acute Overdose

If encountered, gastro-intestinal symptoms and disturbance of the fluid and electrolyte balance may be evident. They may be treated symptomatically and supportive with attention to the water/ electrolyte balance. In the absence of an adequate fluid intake and urinary output, crystalluria is a possibility and the antibiotic may be removed from the circulation by haemodialysis. Oral administration can cause gastro intestinal symptoms such as transient diarrhoea, nausea and colic which are dose related and a result of local irritation not toxicity.

Storage Condition

Store in a cool & dry place protected from light. Amoxicillin suspension and drops should be freshly prepared, stored in a cool dry place preferably in a refrigerator. Reconstituted suspension and drops should be used within 5 days if kept at room temperature or within 7 days if kept in a refrigerator.

Store at 25° C.

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